Journal
JOURNAL OF CELL BIOLOGY
Volume 172, Issue 4, Pages 529-540Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200507081
Keywords
-
Categories
Funding
- NCI NIH HHS [R01 CA077262, CA96985, CA77262, R01 CA096985] Funding Source: Medline
Ask authors/readers for more resources
Aging is a highly complex biological process that is believed to involve multiple mechanisms. Mice that have small amounts of the mitotic checkpoint protein BubR1 age much faster than normal mice, but whether other mitotic checkpoint genes function to prevent the early onset of aging is unknown. In this study, we show that several aging-associated phenotypes appear early in mice that are double haploinsuficient for the mitotic checkpoint genes Bub3 and Rae1 but not in mice that are single haploinsuficient for these genes. Mouse embryonic fibroblasts (MEFs) from Bub3/Rae1 haploinsuficient mice undergo premature senescence and accumulate high levels of p19, p53, p21, and p16, whereas MEFs from single haploinsuficient mice do not. Furthermore, although BubR1 hypomorphic mice have less aneuploidy than Bub3/Rae1 haploinsuficient mice, they age much faster. Our findings suggest that early onset of aging-associated phenotypes in mice with mitotic checkpoint gene defects is linked to cellular senescence and activation of the p53 and p16 pathways rather than to aneuploidy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available